Pulmonary abnormalities at long‐term follow‐up of patients with Langerhans cell histiocytosis

Bernstrand, Cecilia; Cederlund, Kerstin; Sandstedt, Bengt; Åhström, L.; Lundell, Marie; Dahlquist, Gisela; Henter, Jan‐Inge

doi:10.1002/mpo.1110

Cited by 54 publications

(48 citation statements)

References 27 publications

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“…The role of smoking in triggering PLCH was highlighted recently by the finding that most children with systemic LCH who developed PLCH in adolescence or adulthood started to smoke before this event [145]. In addition, in an animal model, one group reported accumulation of LC clusters in mouse lungs exposed to tobacco smoke, but this study has not been reproduced [146].…”

Section: Smoking and Plchmentioning

confidence: 89%

Adult pulmonary Langerhans’ cell histiocytosis

Tazi¹

2006

Eur Respir J

282

297

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Adult pulmonary Langerhans' cell histiocytosis is a rare disorder of unknown aetiology that occurs predominantly in young smokers, with an incidence peak at 20-40 yrs of age. In adults, pulmonary involvement with Langerhans' cell histiocytosis usually occurs as a single-system disease and is characterised by focal Langerhans' cell granulomas infiltrating and destroying distal bronchioles.High-resolution computed tomography (HRCT) of the chest is essential to the diagnosis, typically showing a combination of nodules, cavitated nodules, and thick-and thin-walled cysts. A high macrophage count in bronchoalveolar lavage (BAL) fluid is a common but nonspecific finding that merely reflects exposure to tobacco smoke. BAL is useful for eliminating infections and the other infiltrating lung disorders that can be seen in young adults. Langerhans' cells can be identified in BAL fluid, but, in contrast to what was initially hoped, this test shows a very low sensitivity and is rarely useful in the diagnosis of the disease.The definite diagnosis of pulmonary Langerhans' cell histiocytosis requires identification of Langerhans' cell granulomas, which is usually achieved by surgical lung biopsy at a site selected by chest HRCT. In practice, however, lung biopsy is performed on a case-by-case basis.No effective treatment is available to date, and improved understanding of the mechanisms involved in the pathogenesis of pulmonary Langerhans' cell histiocytosis is urgently needed, and should help in the development of specific therapeutic strategies for patients with this orphan disease.

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Section: Smoking and Plchmentioning

confidence: 89%

Adult pulmonary Langerhans’ cell histiocytosis

Tazi¹

2006

Eur Respir J

282

297

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“…24 An unexpected common finding of concern was liver fibrosis, 25 present at diagnosis in 9 patients and developing subsequently in an additional 9. Seventeen patients had lung fibrosis 26,27 (4 patients at diagnosis and 13 subsequently). CNS radiographic abnormalities, 28 detected in For personal use only.…”

Section: Org Frommentioning

confidence: 99%

Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification

Gadner

Grois

Pötschger

et al. 2008

Blood

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298

219

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Multisystem Langerhans cell histiocytosis (MS-LCH) is associated with high mortality when patients have risk organ involvement (RO ؉)or are younger than 2 years. In an international randomized trial, LCH-II, we intensified their treatment: arm A consisted of 6 weeks of daily prednisone and weekly vinblastine followed by 18 weeks of daily 6-mercaptopurine with vinblastine/prednisone pulses; etoposide was added in arm B. Considering all 193 randomized risk patients, there were similar outcomes: rapid (6 weeks) response (arm A vs arm B: 63%/ 71%), 5-year survival probability (74%/79%), disease reactivation frequency (46%/46%), and permanent consequences (43%/37%). However, (1) patients younger than 2 years without RO involvement (RO ؊ ) had 100% survival and uniformly high (> 80%) rapid response, (2) RO ؉ patients not responding within 6 weeks had highest mortality, and (3) importantly, the more intensive arm B reduced mortality in RO ؉ patients (relative hazard rate, accounting for differences in risk organ involvement, of 0.54; 95% CI ‫؍‬ 0.29-1.00 IntroductionLangerhans cell histiocytosis (LCH) is a reactive clonal proliferation of dendritic cells 1-3 that comprises a wide range of clinical presentations, from localized disease (single-system disease) with excellent outcome to disseminated disease involving 2 and more organs or systems (multisystem disease, MS-LCH). [4][5][6] Treatment has varied from conservative to intensive combination chemotherapy. 7-10 When the systems involved are "risk organs" and/or the patient is younger than 2 years at diagnosis, MS-LCH has been considered particularly devastating, and as carrying a potentially fatal prognosis. 11,12 In 1991, the Histiocyte Society initiated LCH-I, a randomized international clinical trial for MS-LCH, comparing the efficacy of 6-month single-agent therapy with either vinblastine or etoposide (VP-16). 13 The drugs did not differ in disease response, reactivation, permanent consequences, survival, or toxicity. However, the results were inferior in some respects to previous reports based on more aggressive therapy. 8,13 That suggested that therapy for MS-LCH patients should be intensified. We therefore designed the next randomized controlled trial, LCH-II, to evaluate combining vinblastine and VP-16, in an intensified 6-month regimen. Methods Patient entry and randomizationEligible patients (confirmed histopathology, multisystem [MS] disease, age younger than 18 years, and no prior specific therapy) were entered, with informed consent obtained in accordance with the Declaration of Helsinki, from 98 pediatric institutions through 7 study subcenters and stratified into 2 groups, risk and low risk. 14,15 The study and study protocol have been approved by the Institutional Review Board of each institution participating in the trial. The risk patients, the subject of this report, either had involvement of risk organs (RO ϩ ; ie, liver, lung, and hematopoietic system or spleen) or had disease onset at younger than 2 years of age. 11,12 Low-risk MS-LCH patients...

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“…Abundant levels of tumor necrosis factor (TNF)-␣ and other pro-inflammatory cytokines, and the co-stimulatory molecules CD40 and CD40 ligand (CD40L), are seen in LCH lesions (6 -8) thus creating a veritable "cytokine storm" that may account for many of the systemic symptoms in these patients, as well as some of the long-term sequelae (pulmonary abnormalities, CNS dysfunction, etc) (9,10). Moreover, our recent studies have revealed elevated levels of TNF-␣ in the serum of LCH patients (11), and we have shown the addition of anti-TNF-␣ treatment to conventional chemotherapy to be beneficial in a child with severe LCH (12).…”

mentioning

confidence: 99%

Elevated Serum Levels of the Decoy Receptor Osteoprotegerin in Children with Langerhans Cell Histiocytosis

et al. 2006

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Langerhans cell histiocytosis (LCH) is characterized by an accumulation of dendritic Langerhans cells in granulomatous lesions in the bone, skin, and other sites in the body. The pathogenesis of the disease remains unknown. We measured serum levels of the decoy receptor osteoprotegerin (OPG), an important regulator of bone metabolism as well as immune responses, in 18 children with single system (SS) or multi-system (MS) forms of LCH and 20 pediatric controls. OPG levels were significantly increased in LCH patients at diagnosis when compared with controls, and pretreatment levels of OPG were elevated in MS compared with SS patients. Moreover, OPG levels in LCH patients were elevated in patients with involvement of risk organs (liver, lungs, hematopoietic system, or spleen) when compared with patients without risk organ involvement, indicative of an association between OPG values and disease severity. We also observed a positive correlation between serum levels of OPG and tumor necrosis factor (TNF)-␣, a proinflammatory cytokine, at the time of onset of disease. These findings show, for the first time, that serum OPG levels are elevated in LCH patients, and suggest that OPG may play a role in the pathogenesis of this enigmatic disease. (Pediatr Res 59: 281-286, 2006)

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Pulmonary abnormalities at long‐term follow‐up of patients with Langerhans cell histiocytosis

Cited by 54 publications

References 27 publications

Adult pulmonary Langerhans’ cell histiocytosis

Adult pulmonary Langerhans’ cell histiocytosis

Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification

Elevated Serum Levels of the Decoy Receptor Osteoprotegerin in Children with Langerhans Cell Histiocytosis

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